Allicin is responsible for nearly all of each of the several well established pharmacological activities of raw garlic observed in animals. To be able to conduct blinded, placebo-controlled clinical trials, garlic powder supplements have been commonly used. However, much care must be taken in the design of such supplements. It has been known since the 1940s that allicin is not present in raw garlic, but that it is rapidly formed by the enzymatic action of alliinase on alliin when garlic cells are disrupted, such as by crushing. Hence, garlic powders do not contain allicin. They contain alliin and widely varying levels of alliinase, from which allicin can be formed in the body only if alliinase is not inhibited by low gastric pH (inactive below pH 3.5). Gastric pH ranges from 1.5 to 5, depending upon meal conditions. Hence, confidence in allicin formation from supplements can only be achieved by measuring the actual bioavailability of allicin from such products. In the past 30 years, nearly 100 clinical trials have been conducted with garlic supplements, mainly garlic powder tablets, on several cardiovascular risk factors. For every effect there have been substantial conflicts in the trial results, yet not one of these trials has used a supplement for which allicin bioavailability has been determined. Hence, none of the results of these trials can be applied to garlic itself. Objectives: The primary objective of this research is to determine the problematic, and hitherto unknown, human bioavailability of allicin from a variety of commonly consumed garlic powder supplements and garlic foods. Specific aims include determining the bioavailability of allicin (a) from garlic tablets and capsules under meal conditions that will affect the gastric pH (high protein, low protein;timing of supplement consumption, start of meal, end of meal), (b) with respect to the alliinase activity and disintegration time of the supplements, (c) compared to a standard in vitro method for estimating its bioavailability, (d) from cooked (boiled, fried, roasted) garlic, and (e) from commercial garlic foods (pickled, etc.). Design: The bioavailability of allicin from a supplement/food will be determined by comparing the area under the 32-hour concentration curve of breath allyl methyl sulfide (the main metabolite of allicin) to the AUC32 found after consuming homogenized raw garlic of known allicin concentration. Twelve subjects will be tested for each of the 40 planned tests. PUBLIC HEALTH RELEVANCE: This study will provide clinical researchers with the understanding needed to determine what type of supplement should be used in a clinical trial and in what manner it should be consumed, as well as how the results can be extrapolated to crushed raw garlic, all of which are necessary to establish whether or not garlic or garlic supplements can have a health benefit. It will also permit re-evaluation of the clinical trials of the past. It will provide manufacturers a correct standard for the design of supplements. It will provide consumers an awareness of how garlic foods might compare to garlic supplements. This is the most important health research that can be conducted with garlic products. Relevance: This study will provide clinical researchers with the understanding needed to determine what type of supplement should be used in a clinical trial and in what manner it should be consumed, as well as how the results can be extrapolated to crushed raw garlic, all of which are necessary to establish whether or not garlic or garlic supplements can have a health benefit. It will also permit re-evaluation of the clinical trials of the past. It will provide manufacturers a correct standard for the design of supplements. It will provide consumers an awareness of how garlic foods might compare to garlic supplements. This is the most important health research that can be conducted with garlic products.